Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer

Goals: Resistance to cisplatin is the main reason for treatment failure in ovarian cancer. Apoptosis is the main mechanism of action of most cancer chemotherapeutic agents. The apoptosis-associated proteins expressed in cisplatin-sensitive (A2780, COC1) and -resistant (A2780/DDP, COC1/DDP) ovarian cancer cell lines, as well as their effects on caspase-3 activity in these cells, were studied by reverse transcriptase polymerase chain reaction and Western blot analysis. Methods: The apoptotic ratios of A2780, COC1, A2780/DDP, and COC1/DDP cells after treatment with cisplatin were measured by flow cytometry. Results: Expression of Bcl-2 and Bcl-X_L in A2780/DDP and COC1/DDP cells was significantly higher than that in A2780 and COC1 cells, respectively. Expression of Bax and Bcl-Xs did not differ in cisplatin-resistant and -sensitive cells. Caspase-3 activity was reduced markedly and apoptotic ratios were significantly lower in A2780/DDP and COC1/DDP cells than in A2780 and COC1 cells after treatment with cisplatin. Conclusion: We conclude that overexpression of antiapoptotic proteins Bcl-2 and Bcl-X_L and down-regulation of caspase-3 activity may be associated with cisplatin resistance in human ovarian cancer.